Barriers and facilitators to engaging in smoking cessation support among lung screening participants.

INTRODUCTION: Embedded smoking cessation support within lung cancer screening is recommended in the UK; however, little is known about why individuals decline smoking cessation support in this setting. This study identified psychosocial factors that influence smoking cessation and quit motivation among those who declined support for quitting smoking alongside lung cancer screening. METHODS: Qualitative interviews conducted between August 2019 - April 2021 with thirty adults with a smoking history, recruited from the Yorkshire Lung Screening Trial. Participants had declined smoking cessation support. Verbatim interview transcripts were thematically analysed. RESULTS: Fifty percent of participants were male and the majority were from the most deprived groups. Participants reported low motivation and a variety of barriers to stopping smoking. Participants described modifiable behavioural factors that influenced their quit motivation including self-efficacy, perceived effectiveness of stop-smoking services including smoking cessation aids, risk-minimising beliefs, lack of social support, absence of positive influences on smoking and beliefs about smoking/smoking cessation. Broader contextual factors included social isolation and stigma, COVID-19 and comorbid mental and physical health conditions that deterred smoking cessation. CONCLUSIONS: To encourage engagement in smoking cessation support during lung cancer screening, interventions should seek to encourage positive beliefs about the effectiveness of smoking cessation aids and increase confidence in quitting as part of supportive, person-centred care. Interventions should also acknowledge the wider social determinants of health among the lung screening-eligible population. IMPLICATIONS: This study provides an in-depth understanding of the beliefs surrounding smoking and smoking cessation and further potential psychosocial factors that influence those attending lung cancer screening. Many of the barriers to smoking cessation found in the present study are similar to those outside of a lung screening setting however this work offers an understanding of potential facilitators that should be considered in future lung screening programmes.

Alcohol and smoking brief interventions by socioeconomic position: a population-based, cross-sectional study in Great Britain.

BACKGROUND: Alcohol and smoking brief interventions (BIs) in general practice have been shown to be effective in lowering alcohol and smoking-related harm. AIM: To assess prevalence of self-reported BI receipt among increasing or higher-risk drinkers and past-year smokers in England, Scotland, and Wales, and associations between intervention receipt and socioeconomic position. DESIGN & SETTING: Cross-sectional study using data from a monthly population-based survey in England, Scotland, and Wales. METHOD: The study comprised 47 799 participants (15 573 increasing or higher-risk drinkers [alcohol use disorders identification test consumption score ≥5] and 7791 past-year smokers) surveyed via telephone in 2020-2022 (during the COVID-19 pandemic). All data were self-reported. Prevalence of self-reported BI receipt was assessed descriptively; associations between receipt and socioeconomic position were analysed using logistic regression. RESULTS: Among adults in England, Scotland, and Wales, 32.2% (95% confidence interval [CI] = 31.8 to 32.7) reported increasing or higher-risk drinking and 17.7% (95% CI = 17.3 to 18.1) past-year smoking. Among increasing or higher-risk drinkers, 58.0% (95% CI = 57.1 to 58.9) consulted with a GP in the past year, and of these, 4.1% (95% CI = 3.6 to 4.6) reported receiving BIs. Among past-year smokers, 55.8% (95% CI = 54.5 to 57.1) attended general practice in the past year; of these, 41.0% (95% CI = 39.4 to 42.7) stated receiving BIs. There was a tendency for patients from socioeconomically disadvantaged backgrounds to receive more alcohol (adjusted odds ratio [aOR] 1.38, 95% CI = 1.10 to 1.73) or smoking BIs (aOR 1.11, 95% CI = 0.98 to 1.26), but for the latter the results were statistically non-significant. Results did not differ notably by nation within Great Britain. CONCLUSION: BIs in general practice are more common for smoking than for alcohol. A greater proportion of BIs for alcohol were found to be delivered to people who were from socioeconomically disadvantaged backgrounds and who were increasing or higher-risk drinkers.

Impacts of EU Tobacco Products Directive regulations on use of e-cigarettes in adolescents in Great Britain: a natural experiment evaluation.

Background: E-cigarettes are a popular smoking-cessation tool. Although less harmful than tobacco, use of e-cigarettes by non-smokers should be prevented. There is concern about the use of e-cigarettes by young people and that e-cigarettes may renormalise smoking. In May 2016, Tobacco Products Directive regulations aimed to reduce e-cigarettes' appeal to young people. Aims: To examine the effects of the Tobacco Products Directive regulations on young people's use of e-cigarettes, and the role of e-cigarettes in renormalising smoking. Design: A mixed-method natural experimental evaluation combining secondary analyses of survey data, with process evaluation, including interviews with young people, policy stakeholders, retailers and trading standards observers, and observations of retail settings. Settings: Wales, Scotland and England. Participants: Survey participants were aged 13-15 years, living in England, Scotland or Wales and participated in routinely conducted surveys from 1998 to 2019. Process evaluation participants included 14- to 15-year-olds in England, Scotland and Wales, policy stakeholders, trading standards offices and retailers. Intervention: Regulation of e-cigarettes, including bans on cross-border advertising, health warnings and restrictions on product strength. Comparison group: Interrupted time series design, with baseline trends as the comparator. Main outcome measures: The primary outcome was ever e-cigarette use. Secondary outcomes included regular use, ever and regular smoking, smoking attitudes, alcohol and cannabis use. Data capture and analysis: Our primary statistical analysis used data from Wales, including 91,687 young people from the 2013-19 Health Behaviour in School-aged Children and School Health Research Network surveys. In Scotland, we used the Scottish Schools Adolescent Lifestyle and Substance Use Survey and in England we used the Smoking Drinking and Drug Use surveys. The process evaluation included interviews with 73 young people in 2017 and 148 young people in 2018, 12 policy stakeholders, 13 trading standards officers and 27 retailers. We observed 30 retail premises before and after implementation. Data were integrated using the Medical Research Council's process evaluation framework. Results: Ever smoking continued to decline alongside the emergence of e-cigarettes, with a slight slowing in decline for regular use. Tobacco Products Directive regulations were described by stakeholders as well implemented, and observations indicated good compliance. Young people described e-cigarettes as a fad and indicated limited interaction with the components of the Tobacco Products Directive regulations. In primary statistical analyses in Wales [i.e. short (to 2017) and long term (to 2019)], growth in ever use of e-cigarettes prior to Tobacco Products Directive regulations did not continue after implementation. Change in trend was significant in long-term analysis, although of similar magnitude at both time points (odds ratio 0.96). Data from England and Scotland exhibited a similar pattern. Smoking followed the opposite pattern, declining prior to the Tobacco Products Directive regulations, but plateauing as growth in e-cigarette use stalled. Limitations: Alternative causal explanations for changes cannot be ruled out because of the observational design. Conclusions: Young people's ever and regular use of e-cigarettes appears to have peaked around the time of the Tobacco Products Directive regulations and may be declining. Although caution is needed in causal attributions, findings are consistent with an effect of regulations. Our analysis provides little evidence that e-cigarettes renormalise smoking. More recent data indicate that declines in smoking are plateauing. Future work: International comparative work to understand differences in use of e-cigarettes, and tobacco, within varying regulatory frameworks is a priority. Study registration: This study is registered as ResearchRegistry4336. Funding: This project was funded by the National Institute for Health and Care Research (NIHR) Public Health Research programme and will be published in full in Public Health Research; Vol. 11, No. 5. See the NIHR Journals Library website for further project information.

Much has been achieved in preventing young people smoking; however, e-cigarettes have emerged as a new issue. E-cigarettes can help smokers stop, but might also appeal to young people or make smoking look 'normal'. Until recently, In the United Kingdom, there were not many rules for e-cigarettes. In 2016, new rules came in as part of the European Union Tobacco Products Directive regulations. The Tobacco Products Directive regulations limited advertising and included rules about how e-cigarettes should be labelled. In our study, we wanted to know if (1) e-cigarettes make young people think smoking is 'normal' and (2) people's use of e-cigarettes changed after new rules. We included young people who took part in surveys in England, Scotland and Wales between 1998 and 2019. Overall, about 360,000 young people did one of the surveys and about 90,000 were included in our main analysis. We spoke with young people in 2017 and 2018. In addition, in 2018, we spoke with people involved in tobacco policy, trading standards officers and people who sold e-cigarettes. Young people held negative attitudes about smoking and said that friends disagreed with smoking. Young people approved of occasional social e-cigarette use, but not regular use. Stakeholders described a range of views on how e-cigarettes should be regulated. Retailers and trading standards officers said that some retailers did not get much information about Tobacco Products Directive regulations, but new rules were implemented well. The percentage of young people saying that they had tried e-cigarettes was growing, but the number had stopped growing after the new rules. Regular use remained low throughout. Our findings suggest that e-cigarettes are not making smoking look normal again and new rules may have helped stop growth in use of e-cigarettes by young people.

ZIP4 is required for normal progression of synapsis and for over 95% of crossovers in wheat meiosis.

Tetraploid (AABB) and hexaploid (AABBDD) wheat have multiple sets of similar chromosomes, with successful meiosis and preservation of fertility relying on synapsis and crossover (CO) formation only taking place between homologous chromosomes. In hexaploid wheat, the major meiotic gene TaZIP4-B2 (Ph1) on chromosome 5B, promotes CO formation between homologous chromosomes, whilst suppressing COs between homeologous (related) chromosomes. In other species, ZIP4 mutations eliminate approximately 85% of COs, consistent with loss of the class I CO pathway. Tetraploid wheat has three ZIP4 copies: TtZIP4-A1 on chromosome 3A, TtZIP4-B1 on 3B and TtZIP4-B2 on 5B. Here, we have developed single, double and triple zip4 TILLING mutants and a CRISPR Ttzip4-B2 mutant, to determine the effect of ZIP4 genes on synapsis and CO formation in the tetraploid wheat cultivar 'Kronos'. We show that disruption of two ZIP4 gene copies in Ttzip4-A1B1 double mutants, results in a 76-78% reduction in COs when compared to wild-type plants. Moreover, when all three copies are disrupted in Ttzip4-A1B1B2 triple mutants, COs are reduced by over 95%, suggesting that the TtZIP4-B2 copy may also affect class II COs. If this is the case, the class I and class II CO pathways may be interlinked in wheat. When ZIP4 duplicated and diverged from chromosome 3B on wheat polyploidization, the new 5B copy, TaZIP4-B2, could have acquired an additional function to stabilize both CO pathways. In tetraploid plants deficient in all three ZIP4 copies, synapsis is delayed and does not complete, consistent with our previous studies in hexaploid wheat, when a similar delay in synapsis was observed in a 59.3 Mb deletion mutant, ph1b, encompassing the TaZIP4-B2 gene on chromosome 5B. These findings confirm the requirement of ZIP4-B2 for efficient synapsis, and suggest that TtZIP4 genes have a stronger effect on synapsis than previously described in Arabidopsis and rice. Thus, ZIP4-B2 in wheat accounts for the two major phenotypes reported for Ph1, promotion of homologous synapsis and suppression of homeologous COs.

Assessing the profile of support for potential tobacco control policies targeting availability in Great Britain: a cross-sectional population survey.

AIM: To examine the level of support for tobacco availability policies across Great Britain (GB) and associations between support for policy and sociodemographic, smoking and quitting characteristics. METHODS: A cross-sectional representative survey (the Smoking Toolkit Study) of adults in GB (n=2197) during September 2021. Logistic regressions estimated the associations between support for each policy and sociodemographic and smoking characteristics. FINDINGS: There was majority support for requiring retailers to have a license which can be removed if they sell to those under-age (89.6%) and for restrictions on the sale of cigarettes and tobacco near schools (69.9%). More supported than opposed raising the legal age of sale of cigarettes and tobacco to 21 (49.2% supported; 30.7% opposed; 20.1% unsure) and reducing the number of retailers selling tobacco in neighbourhoods with a high density of tobacco retailers (46.5% supported; 23.3% opposed; 30.2% unsure). More opposed than supported a ban on the sale of cigarettes and tobacco to everyone born after a certain year from 2030 onward (a 'tobacco-free generation') (41.3% opposed; 34.5% supported; 24.2% unsure). Age was positively associated with support for raising the age of sale and inversely associated with requiring tobacco retailer licenses. Women were more likely to support raising the age of sale and reducing the number of retailers. CONCLUSIONS: Requiring tobacco retailer licensing and restrictions on sales near schools received majority support. Other tobacco availability policies received substantial support despite considerable opposition.

Actions of Novel Angiotensin Receptor Blocking Drugs, Bisartans, Relevant for COVID-19 Therapy: Biased Agonism at Angiotensin Receptors and the Beneficial Effects of Neprilysin in the Renin Angiotensin System.

Angiotensin receptor blockers (ARBs) used in the treatment of hypertension and potentially in SARS-CoV-2 infection exhibit inverse agonist effects at angiotensin AR1 receptors, suggesting the receptor may have evolved to accommodate naturally occurring angiotensin 'antipeptides'. Screening of the human genome has identified a peptide (EGVYVHPV) encoded by mRNA, complementary to that encoding ANG II itself, which is an inverse agonist. Thus, opposite strands of DNA encode peptides with opposite effects at AR1 receptors. Agonism and inverse agonism at AR1 receptors can be explained by a receptor 'switching' between an activated state invoking receptor dimerization/G protein coupling and an inverse agonist state mediated by an alternative/second messenger that is slow to reverse. Both receptor states appear to be driven by the formation of the ANG II charge-relay system involving TyrOH-His/imidazole-Carboxylate (analogous to serine proteases). In this system, tyrosinate species formed are essential for activating AT1 and AT2 receptors. ANGII is also known to bind to the zinc-coordinated metalloprotease angiotensin converting enzyme 2 (ACE2) used by the COVID-19 virus to enter cells. Here we report in silico results demonstrating the binding of a new class of anionic biphenyl-tetrazole sartans ('Bisartans') to the active site zinc atom of the endopeptidase Neprilysin (NEP) involved in regulating hypertension, by modulating humoral levels of beneficial vasoactive peptides in the RAS such as vasodilator angiotensin (1-7). In vivo and modeling evidence further suggest Bisartans can inhibit ANG II-induced pulmonary edema and may be useful in combatting SARS-CoV-2 infection by inhibiting ACE2-mediated viral entry to cells.

Health behaviour change among UK adults during the pandemic: findings from the COVID-19 cancer attitudes and behaviours study.

BACKGROUND: COVID-19 related lockdowns may have affected engagement in health behaviours among the UK adult population. This prospective observational study assessed socio-demographic patterning in attempts to change and maintain a range of health behaviours and changes between two time points during the pandemic. METHODS: Adults aged 18 years and over (n = 4,978) were recruited using Dynata (an online market research platform) and the HealthWise Wales platform, supplemented through social media advertising. Online surveys were conducted in August/September 2020 when lockdown restrictions eased in the UK following the first major UK lockdown (survey phase 1) and in February/March 2021 during a further national lockdown (survey phase 2). Measures derived from the Cancer Awareness Measure included self-reported attempts to reduce alcohol consumption, increase fruit/vegetable consumption, increase physical activity, lose weight and reduce/stop smoking. Multivariable logistic regressions were used to assess individual health behaviour change attempts over time, adjusted for age, sex, ethnicity, employment and education. RESULTS: Around half of participants in survey phase 1 reported trying to increase physical activity (n = 2607, 52.4%), increase fruit/vegetables (n = 2445, 49.1%) and lose weight (n = 2413, 48.5%), with 19.0% (n = 948) trying to reduce alcohol consumption among people who drink. Among the 738 participants who smoked, 51.5% (n = 380) were trying to reduce and 27.4% (n = 202) to stop smoking completely. Most behaviour change attempts were more common among women, younger adults and minority ethnic group participants. Efforts to reduce smoking (aOR: 0.98, 95% CI: 0.82-1.17) and stop smoking (aOR: 0.98, 95% CI: 0.80-1.20) did not differ significantly in phase 2 compared to phase 1. Similarly, changes over time in attempts to improve other health behaviours were not statistically significant: physical activity (aOR: 1.07; 95% CI: 0.99-1.16); weight loss (aOR: 0.95; 95% CI: 0.90-1.00); fruit/vegetable intake (aOR: 0.98, 95% CI: 0.91-1.06) and alcohol use (aOR: 1.32, 95% CI: 0.92-1.91). CONCLUSION: A substantial proportion of participants reported attempts to change health behaviours in the initial survey phase. However, the lack of change observed over time indicated that overall motivation to engage in healthy behaviours was sustained among the UK adult population, from a period shortly after the first lockdown toward the end of the second prolonged lockdown.

Understanding the Driving Forces That Trigger Mutations in SARS-CoV-2: Mutational Energetics and the Role of Arginine Blockers in COVID-19 Therapy.

SARS-CoV-2 is a global challenge due to its ability to mutate into variants that spread more rapidly than the wild-type virus. Because the molecular biology of this virus has been studied in such great detail, it represents an archetypal paradigm for research into new antiviral drug therapies. The rapid evolution of SARS-CoV-2 in the human population is driven, in part, by mutations in the receptor-binding domain (RBD) of the spike (S-) protein, some of which enable tighter binding to angiotensin-converting enzyme (ACE2). More stable RBD-ACE2 association is coupled with accelerated hydrolysis of furin and 3CLpro cleavage sites that augment infection. Non-RBD and non-interfacial mutations assist the S-protein in adopting thermodynamically favorable conformations for stronger binding. The driving forces of key mutations for Alpha, Beta, Gamma, Delta, Kappa, Lambda and Omicron variants, which stabilize the RBD-ACE2 complex, are investigated by free-energy computational approaches, as well as equilibrium and steered molecular dynamic simulations. Considered also are the structural hydropathy traits of the residues in the interface between SARS-CoV-2 RBD and ACE2 protein. Salt bridges and π-π interactions are critical forces that create stronger complexes between the RBD and ACE2. The trend of mutations is the replacement of non-polar hydrophobic interactions with polar hydrophilic interactions, which enhance binding of RBD with ACE2. However, this is not always the case, as conformational landscapes also contribute to a stronger binding. Arginine, the most polar and hydrophilic among the natural amino acids, is the most aggressive mutant amino acid for stronger binding. Arginine blockers, such as traditional sartans that bear anionic tetrazoles and carboxylates, may be ideal candidate drugs for retarding viral infection by weakening S-protein RBD binding to ACE2 and discouraging hydrolysis of cleavage sites. Based on our computational results it is suggested that a new generation of "supersartans", called "bisartans", bearing two anionic biphenyl-tetrazole pharmacophores, are superior to carboxylates in terms of their interactions with viral targets, suggesting their potential as drugs in the treatment of COVID-19. In Brief: This in silico study reviews our understanding of molecular driving forces that trigger mutations in the SARS-CoV-2 virus. It also reports further studies on a new class of "supersartans" referred to herein as "bisartans", bearing two anionic biphenyltetrazole moieties that show potential in models for blocking critical amino acids of mutants, such as arginine, in the Delta variant. Bisartans may also act at other targets essential for viral infection and replication (i.e., ACE2, furin cleavage site and 3CLpro), rendering them potential new drugs for additional experimentation and translation to human clinical trials.

Discovery of a new generation of angiotensin receptor blocking drugs: Receptor mechanisms and in silico binding to enzymes relevant to SARS-CoV-2.

The discovery and facile synthesis of a new class of sartan-like arterial antihypertensive drugs (angiotensin receptor blockers [ARBs]), subsequently referred to as "bisartans" is reported. In vivo results and complementary molecular modelling presented in this communication indicate bisartans may be beneficial for the treatment of not only heart disease, diabetes, renal dysfunction, and related illnesses, but possibly COVID-19. Bisartans are novel bis-alkylated imidazole sartan derivatives bearing dual symmetric anionic biphenyl tetrazole moieties. In silico docking and molecular dynamics studies revealed bisartans exhibited higher binding affinities for the ACE2/spike protein complex (PDB 6LZG) compared to all other known sartans. They also underwent stable docking to the Zn2 + domain of the ACE2 catalytic site as well as the critical interfacial region between ACE2 and the SARS-CoV-2 receptor binding domain. Additionally, semi-stable docking of bisartans at the arginine-rich furin-cleavage site of the SARS-CoV-2 spike protein (residues 681-686) required for virus entry into host cells, suggest bisartans may inhibit furin action thereby retarding viral entry into host cells. Bisartan tetrazole groups surpass nitrile, the pharmacophoric "warhead" of PF-07321332, in its ability to disrupt the cysteine charge relay system of 3CLpro. However, despite the apparent targeting of multifunctional sites, bisartans do not inhibit SARS-CoV-2 infection in bioassays as effectively as PF-07321332 (Paxlovid).

Prevalence of Menthol and Menthol Capsule Cigarette Use Among 11-16 Year Olds in Wales Prior to a Ban on Characterizing Flavors in Cigarettes: Findings From the 2019 Student Health and Wellbeing Survey.

INTRODUCTION: The use of flavored cigarettes has increased in many countries because of the inclusion of one or more frangible flavor-changing capsules in the filter. Research suggests that these "capsule" cigarettes appeal most to youth, but little is known about how prevalent their use is among children. METHODS: A cross-sectional school survey was conducted between September and December 2019 with 11-16 year-olds (N = 119 388) from 198 secondary schools across Wales; the sample represented approximately two-thirds of all 11-16 year-olds in the country. The sample was asked about smoking behavior, with a quarter (N = 26 950) also asked about awareness of menthol cigarettes, and use of menthol and menthol capsule cigarettes if a current smoker (N = 1447). RESULTS: Current smoking prevalence was 5.7% among the entire sample and 5.9% among the analytical sample (those also asked about menthol and menthol capsule cigarettes). For the analytical sample, almost all current smokers (93.2%) were aware of menthol cigarettes, with three-fifths (60.5%) reporting having used menthol cigarettes in the past 30 days (42.3% capsule cigarettes, 18.2% noncapsule cigarettes). In comparison to nonmenthol smokers, those using menthol cigarettes (capsule and noncapsule) were more likely to be frequent smokers, with those using menthol capsule cigarettes more likely to have smoked for longer. CONCLUSIONS: While past research suggests that flavored cigarettes appeal to youth, this study shows just how popular these products, and capsule cigarettes, in particular, were among young smokers in Wales. It also raises questions about why capsule cigarettes have received such limited public health attention. IMPLICATIONS: That three in five 11-16 year-old smokers reported using menthol cigarettes in the past 30 days highlights how appealing these products are to young people, particularly capsule cigarettes, used by seventy percent of menthol smokers. Capsule cigarettes are one of the most successful tobacco product innovations in decades, even in countries with comprehensive bans on tobacco marketing and standardized packaging. The dearth of research on capsule cigarettes is a failure of global public health. Evaluation of the ban on characterizing flavors in the United Kingdom and across the European Union is critical.

Tobacco use, smoking identities and pathways into and out of smoking among young adults: a meta-ethnography.

BACKGROUND: This meta-ethnography investigates how young adults describe their tobacco use, smoking identities and pathways into and out of regular smoking, to inform future smoking prevention and harm reduction interventions. METHODS: Eight databases were systematically searched using keywords and indexed terms. Studies were included if they presented qualitative data from young adults aged 16-25 reporting smoking histories and/or smoking identities from countries culturally similar to the UK. A systematic and rigorous meta-ethnographic approach was employed, consistent with Noblit and Hare's methodology. RESULTS: Thirty papers were included. Reasons stated for taking up smoking and becoming a smoker included alleviating stress, transforming one's identity, and coping with the transition to further education, employment or leaving home. Many used smoking to aid acceptance within new peer groups, particularly when alcohol was present. Smoking was also perceived as an act of resistance and a coping mechanism for those with marginalised identities. Barriers to quitting smoking included young adults' minimisation or denial of the health risks of smoking and not identifying with "being a smoker". CONCLUSIONS: This meta-ethnography may provide a blueprint to inform the development of health and wellbeing interventions designed specifically for young adults. Smoking cessation interventions should be co-designed with young adults based on their perceived needs, resonant with their desire to quit in the future at key milestones. Harm reduction interventions should address the social aspect of addiction, without reinforcing stigma, particularly for those with marginalised identities.

Inequalities in Smoking and Quitting-Related Outcomes Among Adults With and Without Children in the Household 2013-2019: A Population Survey in England.

INTRODUCTION: Smoking among those who live with children is an important influence on smoking initiation among children. This study assessed socioeconomic inequalities in smoking and quitting-related outcomes among all adults with and without children in the household. AIMS AND METHODS: Monthly repeat cross-sectional household survey of adults (16+) from 2013-2019 in England (N = 138 583). We assessed the association between cigarette smoking and quitting-related outcomes and having children in the household, and whether these relationships were moderated by occupational social grade (categories AB-E from most to least advantaged). Trends in smoking prevalence among adults with and without children in the household were explored. RESULTS: In adjusted analysis, the association of having children in the household with smoking prevalence depended on social grade: smoking prevalence was between 0.71 (95% confidence interval 0.66-0.77) and 0.93 (0.88-0.98) times lower among social grades AB-D with children in the household relative to those without. Conversely, it was 1.11 (1.05-1.16) times higher among social grade E. Yearly prevalence declined similarly among those with and without children (both prevalence ratio: 0.98, 95% confidence interval 0.97-0.99). Motivation to stop smoking was higher among those with children than those without, but lower among disadvantaged than more advantaged groups. Social grades D-E had greater heavy smoking, but higher prevalence of past-month quit attempts. CONCLUSIONS: Among the most disadvantaged social grade in England, smoking prevalence was higher in those with children in the household than without. To attenuate future smoking-related inequalities, there is an urgent need to target support and address barriers to quitting and promote longer-term quit success. IMPLICATIONS: In the most disadvantaged occupational social grade, having children in the household was associated with higher smoking prevalence compared with not having children. This contrasts with all other social grades in which there was lower comparative smoking prevalence among those with than without children in the household. Without attention this disparity could exacerbate existing and future health inequalities related to smoking.

A separation-of-function ZIP4 wheat mutant allows crossover between related chromosomes and is meiotically stable.

Many species, including most flowering plants, are polyploid, possessing multiple genomes. During polyploidisation, fertility is preserved via the evolution of mechanisms to control the behaviour of these multiple genomes during meiosis. On the polyploidisation of wheat, the major meiotic gene ZIP4 duplicated and diverged, with the resulting new gene TaZIP4-B2 being inserted into chromosome 5B. Previous studies showed that this TaZIP4-B2 promotes pairing and synapsis between wheat homologous chromosomes, whilst suppressing crossover between related (homoeologous) chromosomes. Moreover, in wheat, the presence of TaZIP4-B2 preserves up to 50% of grain number. The present study exploits a 'separation-of-function' wheat Tazip4-B2 mutant named zip4-ph1d, in which the Tazip4-B2 copy still promotes correct pairing and synapsis between homologues (resulting in the same pollen profile and fertility normally found in wild type wheat), but which also allows crossover between the related chromosomes in wheat haploids of this mutant. This suggests an improved utility for the new zip4-ph1d mutant line during wheat breeding, compared to the previously described CRISPR Tazip4-B2 and ph1 mutant lines. The results also reveal that loss of suppression of homoeologous crossover between wheat chromosomes does not in itself reduce wheat fertility when promotion of homologous pairing and synapsis by TaZIP4-B2 is preserved.

Changes in childhood experimentation with, and exposure to, tobacco and e-cigarettes and perceived smoking norms: a repeated cross-sectional study of 10-11 year olds' in Wales.

BACKGROUND: Today's primary school children have grown up in a climate of strong smoking restrictions, decreasing tobacco use, and the emergence of e-cigarettes. Children's exposure to tobacco declined substantially in years following the introduction of smoke-free legislation, with smoking uptake and perceived smoking norms declining. There is debate regarding whether emergence of e-cigarettes may interrupt trends in children's smoking perceptions, or offer a means for adults to limit children's exposure to tobacco. This study examines change in children's tobacco and e-cigarettes experimentation (ever use), exposure to secondhand smoking and vaping, and perceived smoking norms. METHODS: Data from four, repeat cross-sectional surveys of Year 6 primary school pupils (age 10-11 years) in Wales in 2007, 2008, 2014 and 2019 (n = 6741) were combined. E-cigarette use and perceptions were included in 2014 and 2019 surveys. Analyses used binary logistic regression analyses, adjusted for school-level clustering. RESULTS: Child tobacco experimentation and most indicators of exposure to tobacco smoke indicated a graded decreasing trend over time from 2007 to 2019. Exposure to e-cigarettes increased from 2014 to 2019, as did pupil awareness of e-cigarettes (OR = 2.56, 95%CI = 2.12-3.10), and parental use (OR = 1.26, 95%CI = 1.00-1.57). A decrease in child e-cigarette experimentation was not significant (OR = 0.80, 95%CI = 0.57-1.13). Children's normative perceptions for smoking by adults and children indicated a graded decrease over time (OR = 0.66, 95%CI = 0.54-0.80; OR = 0.69, 95%CI = 0.55-0.86; respectively from 2014 to 2019). However, fewer reported disapproval of people smoking around them in 2019 relative to 2014 (OR = 0.68, 95%CI = 0.53-0.88). Higher exposure to tobacco cigarettes and e-cigarettes in public places, cars and households were associated with favourable normative perceptions for tobacco smoking; however in models adjusted for exposure to both associations of e-cigarette exposure were attenuated. CONCLUSION: Children's experimentation with and exposure to tobacco, and their perceptions of smoking as a normative behaviour, have continued to decline alongside growth in exposure to e-cigarettes. Although a large majority of pupils reported they minded people smoking around them, there was some evidence of diminishing disapproval of secondhand smoke since 2007. Further research is needed to understand whether use of e-cigarettes in cars and homes is displacing prior smoking or being introduced into environments where smoking had been eliminated.

Intentions to participate in cervical and colorectal cancer screening during the COVID-19 pandemic: A mixed-methods study.

Worldwide, cancer screening faced significant disruption in 2020 due to the COVID-19 pandemic. If this has led to changes in public attitudes towards screening and reduced intention to participate, there is a risk of long-term adverse impact on cancer outcomes. In this study, we examined previous participation and future intentions to take part in cervical and colorectal cancer (CRC) screening following the first national lockdown in the UK. Overall, 7543 adults were recruited to a cross-sectional online survey in August-September 2020. Logistic regression analyses were used to identify correlates of strong screening intentions among 2319 participants eligible for cervical screening and 2502 eligible for home-based CRC screening. Qualitative interviews were conducted with a sub-sample of 30 participants. Verbatim transcripts were analysed thematically. Of those eligible, 74% of survey participants intended to attend cervical screening and 84% intended to complete home-based CRC screening when next invited. Thirty percent and 19% of the cervical and CRC samples respectively said they were less likely to attend a cancer screening appointment now than before the pandemic. Previous non-participation was the strongest predictor of low intentions for cervical (aOR 26.31, 95% CI: 17.61-39.30) and CRC (aOR 67.68, 95% CI: 33.91-135.06) screening. Interview participants expressed concerns about visiting healthcare settings but were keen to participate when screening programmes resumed. Intentions to participate in future screening were high and strongly associated with previous engagement in both programmes. As screening services recover, it will be important to monitor participation and to ensure people feel safe to attend.

Cancer symptom experience and help-seeking behaviour during the COVID-19 pandemic in the UK: a cross-sectional population survey.

OBJECTIVES: To understand self-reported potential cancer symptom help-seeking behaviours and attitudes during the first 6 months (March-August 2020) of the UK COVID-19 pandemic. DESIGN: UK population-based survey conducted during August and September 2020. Correlates of help-seeking behaviour were modelled using logistic regression in participants reporting potential cancer symptoms during the previous 6 months. Qualitative telephone interviews with a purposeful subsample of participants, analysed thematically. SETTING: Online UK wide survey. PARTICIPANTS: 7543 adults recruited via Cancer Research UK online panel provider (Dynata) and HealthWise Wales (a national register of 'research ready' participants) supplemented with social media (Facebook and Twitter) recruitment. 30 participants were also interviewed. MAIN OUTCOME MEASURES: Survey measures included experiences of 15 potential cancer symptoms, help-seeking behaviour, barriers and prompts to help-seeking. RESULTS: Of 3025 (40.1%) participants who experienced a potential cancer symptom, 44.8% (1355/3025) had not contacted their general practitioner (GP). Odds of help-seeking were higher among participants with disability (adjusted OR (aOR)=1.38, 95% CI 1.11 to 1.71) and who experienced more symptoms (aOR=1.68, 95% CI 1.56 to 1.82), and lower among those who perceived COVID-19 as the cause of symptom(s) (aOR=0.36, 95% CI 0.25 to 0.52). Barriers included worries about wasting the doctor's time (1158/7543, 15.4%), putting strain on healthcare services (945, 12.6%) and not wanting to make a fuss (907, 12.0%). Interviewees reported reluctance to contact the GP due to concerns about COVID-19 and fear of attending hospitals, and described putting their health concerns on hold. CONCLUSIONS: Many people avoided healthcare services despite experiencing potential cancer symptoms during the COVID-19 pandemic. Alongside current help-seeking campaigns, well-timed and appropriate nationally coordinated campaigns should signal that services are open safely for those with unusual or persistent symptoms. TRIAL REGISTRATION NUMBER: ISRCTN17782018.

Protocol for expansion of an existing national monthly survey of smoking behaviour and alcohol use in England to Scotland and Wales: The Smoking and Alcohol Toolkit Study.

Background The Smoking and Alcohol Toolkit Study (STS/ATS) in England has delivered timely insights to inform and evaluate strategies aimed at reducing tobacco smoking- and alcohol-related harm. From the end of 2020 until at least 2024 the STS/ATS is expanding to Scotland and Wales to include all constituent nations in Great Britain. Expanding data collection to Scotland and Wales will permit the evaluation of how smoking and alcohol related behaviours respond to divergent policy scenarios across the devolved nations. Methods The STS/ATS consists of monthly cross-sectional household interviews (computer or telephone assisted) of representative samples of adults in Great Britain aged 16+ years. Commencing in October 2020 each month a new sample of approximately 1700 adults in England, 450 adults in Scotland and 300 adults in Wales complete the survey (~n = 29,400 per year). The expansion of the survey to Scotland and Wales has been funded for the collection of at least 48 waves of data across four years. The data collected cover a broad range of smoking and alcohol-related parameters (including but not limited to smoking status, cigarette/nicotine dependence, route to quit smoking, prevalence and frequency of hazardous drinking, attempts and motivation to reduce alcohol consumption, help sought and motives for attempts to reduce alcohol intake) and socio-demographic characteristics (including but not limited to age, gender, region, socio-economic position) and will be reviewed monthly and refined in response to evolving policy needs and public interests. All data analyses will be pre-specified and available on a free online platform. A dedicated website will publish descriptive data on important trends each month. Discussion The Smoking and Alcohol Toolkit Study will provide timely monitoring of smoking and alcohol related behaviours to inform and evaluate national policies across Great Britain.

Using Latent Class Analysis to Explore Complex Associations Between Socioeconomic Status and Adolescent Health and Well-Being.

PURPOSE: Research demonstrates a strong socioeconomic gradient in health and well-being. However, many studies rely on unidimensional measures of socioeconomic status (SES) (e.g. educational qualifications, household income), and there is often a more limited consideration of how facets of SES combine to impact well-being. This paper develops a multidimensional measure of SES, drawing on family and school-level factors, to provide more nuanced understandings of socioeconomic patterns in adolescent substance use and mental well-being. METHODS: Data from the Student Health and Wellbeing Survey from Wales, UK was employed. The sample compromised 22,372 students and we used latent class analysis to identify distinct groups using three measures of SES. These classes were then used to estimate mental well-being, internalizing symptoms, and substance use. RESULTS: The five-class solution offered the best fit. Findings indicated distinct classes of families as follows: "nonworking," "deprived working families," "affluent families in deprived schools," "lower affluence," and "higher affluence." There was a clear relationship among the classes and mental well-being, internalizing symptoms, smoking, and cannabis use; alcohol was the exception to this. CONCLUSIONS: The identification of these classes led to a fuller understanding of the health and well-being effects of SES, showing clearer patterning in health behaviors that often is not captured in research. The implications for adolescent health and well-being are discussed, including considerations for future research.

Smoking, distress and COVID-19 in England: Cross-sectional population surveys from 2016 to 2020.

Changes in the prevalence of psychological distress among smokers during the COVID-19 pandemic in England may exacerbate existing health inequalities. This study examined the prevalence of psychological distress among smokers following the onset of the pandemic compared with previous years. Cross-sectional data came from a representative survey of smokers (18+) in England (n = 2,927) between April-July in 2016, 2017 and 2020. Logistic regressions estimated the associations between past-month distress across 2016/2017 and 2020, and age. Weighted proportions, chi-squared statistics and stratified logistic regression models were used to compare the distributions of moderate and severe distress, respectively, within socio-demographic and smoking characteristics in 2016/2017 and 2020. Between the combined April-July 2016 and 2017 sample and April-July 2020 the prevalence of moderate and severe distress among past-year smokers increased (2016/2017: moderate 20.66%, 19.02-22.43; severe 8.23%, 7.16-9.47; 2020: moderate 28.79%, 95%CI 26.11-31.60; OR = 2.08, 95%CI 1.34-3.25; severe 11.04%, 9.30-13.12; OR = 2.16, 1.13-4.07). While there was no overall evidence of an interaction between time period and age, young (16-24 years) and middle-age groups (45-54 years) may have experienced greater increases in moderate distress and older age groups (65+ years) increases in severe distress. There were increases of moderate distress among more disadvantaged social grades and both moderate and severe distress among women and those with low cigarette addiction. Between April-July 2016/2017 and April-July 2020 in England there were increases in both moderate and severe distress among smokers. The distribution of distress among smokers differed between 2016/2017 and 2020 and represents a widening of inequalities.

Psychosocial determinants of quit motivation in older smokers from deprived backgrounds: a cross-sectional survey.

OBJECTIVES: To identify psychosocial determinants of quit motivation in older deprived smokers. The evidence may be used to optimise smoking cessation interventions for the target population. DESIGN: Cross-sectional survey using online recruitment methods including Facebook-targeted advertising. SETTING: UK, 2019. PARTICIPANTS: Current smokers aged 50 years or older and from a socioeconomically deprived background. MAIN OUTCOME MEASURES: Measures included motivation to stop smoking, smoking history, perceived social support, self-efficacy for quitting, self-exempting beliefs and lung cancer risk perception. Multivariable regression was used to analyse factors associated with quit motivation. RESULTS: Of a total 578 individuals who consented to take part, 278 (48.1%) did not meet the inclusion criteria. Of the 300 eligible participants, most were recruited using Facebook (94.0%), were aged 50-64 years (83.7%) and women (85.7%). Most participants were renting from a housing association (72.0%) and had low education (61.0%). Higher motivation to quit was statistically significantly associated with a higher intensity of previous quit attempts (p=0.03), higher quit confidence (p=0.01), higher smoking self-efficacy (p=0.01), a lower risk-minimising beliefs score (p=0.01) and using traditional nicotine replacement therapy (NRT) when trying to stop smoking or cut down (p<0.001). CONCLUSION: Older smokers from deprived backgrounds face complex barriers to quitting smoking. Interventions are needed to increase self-efficacy for quitting, modify risk-minimising beliefs and target elements of previous quit attempts (ie, the use of NRT) that are associated with motivation to stop smoking.